Head and neck cancer is one of the leading causes of cancer-related deaths worldwide, and squamous cell carcinomas (HNSCC) account for the majority of cases. In a new study, published on July 29, 2020, in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research. Researchers from The University of California San Diego School of Medicine and Moores Cancer Center report that an experimental drug called tipifarnib has shown promise in treating HNSCC tumors with mutations in the HRAS gene.
Findings from the study shed new light on the HRAS gene, a gene that produces proteins that regulate a variety of cellular processes, including growth, movement, and differentiation. In 4 to 8 percent of HNSCC tumors, the HRAS gene is mutated.
J. Silvio Gutkind, Ph.D., Professor of Pharmacology and associate director of basic science at UC San Diego Moores Cancer Center states,
“This preclinical research has the potential to extend to the entire HNSCC patient community, whose overall survival rates are limited in recurrent or metastatic disease, and existing therapeutic options that are far from optimal, with response rates of roughly 10 to 20 percent.” He continued,
“These preclinical findings support the idea that HRAS represents a druggable oncogene in HNSCC. Tipifarnib is a selective inhibitor of farnesyltransferase, an enzyme that plays a critical role in anchoring some RAS family proteins to cellular membranes .”
In the study, UC San Diego researchers found that cell line – and patient-derived HNSCC models harboring HRAS mutations were highly sensitive to tipifarnib.
Currently, Kura Oncology, a San Diego-based biopharmaceutical company, is conducting a nationwide clinical trial to assess the safety and efficacy of tipifarnib in head and neck cancer with HRAS mutations.
According to the study’s authors, treatment with tipifarnib has a multifaceted effect on the biology of HRAS-mutant HNSCC tumors. They assist in reducing oncogenic signaling and proliferation. They also increase apoptosis (cell death), thus blocking angiogenesis (development of new blood vessels in tumors) and driving squamous differentiation of tumors.
The results of the study are significant because there are approximately 650,000 cases and 330,000 deaths annually worldwide from head and neck cancer. In the United States, alone roughly 4 percent of all cancers are head and neck, with an estimated 65,630 persons diagnosed each year, two-thirds of them men and 14,500 deaths, according to Cancer.Net.
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